Diet, Cancer and Public Health

Lead Research Organisation: Medical Research Council

Abstract

This work is aimed at establishing that aspects of diet, as modulated by individual inherited genetic factors, result in damage to DNA, and changes in hormone levels, that may be important in the causation of cancer in humans. Controlled feeding studies in humans are carried out to establish the effects of diet on cellular metabolism, for example, the effect of meat and other dietary factors on endogenous N- nitrosation within the colon and the formation of alkylative adducts and mutations in colonic exfoliated cells and biopsy tissue, in collaboration with other Universities. Recruitment for the European Prospective Investigation of Cancer (EPIC) a large free living cohort of 25,000 people, in which the dietary habits are being measured and the occurrence of cancer is being documented, has been completed in collaboration with The Institute of Public Health in Cambridge, the International Agency for Research in Lyon, France, and othr participating cohorts in Europe. Studies on the interaction of diet, phytoestrogens, hormones and genotype are ongoing in cancer cases and controls. Interactions with diet and genes controlling steroid hormone metabolism are also being assessed.

Technical Summary

Aims (i) To determine gene nutrient interactions relating large intestinal risk factors to markers of DNA damage in the colorectal lumen (ii) Quantitative determination of risks to humans from nutritional habits in cancers of breast and bowel and cardiovascular disease and interactions with gene variants (iii) To assess biological effects of plant oestrogens, in relation to breast, colon and prostate cancer. Methodology (i) Controlled human feeding studies in healthy volunteers of known genotype to determine effects of dietary changes on intestinal N-nitrosation and cancer related markers of DNA damage in exfoliated cells, biopsies and lymphocytes. (ii) Prospective study of presently healthy 45 to 75 y men and women followed over 10 - 20 years as part of EPIC, (European Prospective Investigation of Cancer). Lifetime dietary habits of individuals who develop cancer and those who do not will be differentiated, thus allowing quantitative estimates of risk from diet in cancer at the different sites in relation to genotype. (iii) Development of biological markers of nutritional intake to enable measurement errors associated with nutritional assessment to be assessed. Some of these markers may be useful for compliance in clinical studies (iv)LC/MS techniques have been developed to measure contents of lignans and isoflavones in foods and biological specimens in order to determine the metabolism and biological effects of these compounds, and interaction with gene variants controlling sex hormone metabolism and prospective assessment in (ii) in breast, colon and prostate cancer.

Publications

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Bingham S (2006) The fibre-folate debate in colo-rectal cancer. in The Proceedings of the Nutrition Society

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Dahm CC (2010) Dietary fiber and colorectal cancer risk: a nested case-control study using food diaries. in Journal of the National Cancer Institute

 
Description NDNS
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact Food Standards Agency - National Diet and Nutrition Survey
 
Description SACN
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact Scientific Advisory Committee on Nutrition
 
Description MRC Centre Grant
Amount £2,400,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 05/2006 
End 05/2012
 
Title PABA 
Description Developed the use of PABA in validating 24hr urine collection 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2006 
Provided To Others? Yes  
Impact The use of PABA has increased the accuracy of studies using 24 urine collection 
 
Description Addenbrookes 
Organisation Addenbrooke's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution Support in study design and protocol.
Collaborator Contribution Allowing contribution to NHS Bowel Screening Pilot
Impact Various publications
Start Year 2007
 
Description Pathology 
Organisation University of Cambridge
Department Department of Pathology
Country United Kingdom 
Sector Academic/University 
PI Contribution Various post-doc and phd research undertaken in mutations in colorectal cancer tissue, colonic biopsies and microarrays, and markers of DNA damage in the colon within this collaboration
Collaborator Contribution Technical lab support and supervisory support
Impact Various publications, and more recently the successful completion of PhD's by Laura Gay and Adam Naguib
 
Description University of Reading 
Organisation University of Reading
Department Department of Food and Nutritional Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution In his new role at redaing, and under his Honorary Contract with the CNC, Univeristy of Cambridge, Dr Gunter Kuhlne is contining work on Diet & Cancer samples.
Impact Ethics applications in progress
Start Year 2010
 
Description Away Day - Cambridge 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Primary Audience Participants in your research and patient groups
Results and Impact The Unit presented current work to the CNC group.

Provided a valuable forum to share and bring together current work, and enabled valuable feedback from Profs. Kay Tee Khaw and John Potter.
Year(s) Of Engagement Activity 2008